Antibiotics: New recipe for targeting resistance

October 18th, 2016 by Balázs Papp

Nature Chemical Biology 12, 891 (2016). doi:10.1038/nchembio.2215

Authors: Balázs Papp & Viktória Lázár

The rapid spread of antibiotic-resistant bacteria demands novel treatment approaches that delay or even reverse the evolution of resistance. A new screening strategy identifies two compounds that select against a common tetracycline-resistance gene in Escherichia coli.

Enzyme mechanisms: Sugary shears

October 18th, 2016 by Ethan D Goddard-Borger

Nature Chemical Biology 12, 892 (2016). doi:10.1038/nchembio.2216

Author: Ethan D Goddard-Borger

Proteolytic maturation of an important transcriptional regulator is performed by a glycosyltransferase. The reaction involves glycosylation of a glutamate residue and conversion of the γ-glycosyl ester product into an N-acyl pyroglutamate, which undergoes spontaneous hydrolysis to effect peptide backbone fission.

Metabolic engineering: Biosensors get the green light

October 18th, 2016 by Sarah K Hammer

Nature Chemical Biology 12, 894 (2016). doi:10.1038/nchembio.2214

Authors: Sarah K Hammer & José L Avalos

A novel approach recruits the largest prokaryotic family of ligand-induced transcriptional regulators to develop a new class of biosensors in yeast based on transcriptional activation, vastly expanding the repertoire of biosensors that could function in eukaryotic hosts.

Synthetic biology: Cholera detectors

October 18th, 2016 by Caitlin Deane

Nature Chemical Biology 12, 889 (2016). doi:10.1038/nchembio.2222

Author: Caitlin Deane

Proteomics: Fishing for zinc

October 18th, 2016 by Grant Miura

Nature Chemical Biology 12, 889 (2016). doi:10.1038/nchembio.2220

Author: Grant Miura

Protein dynamics: Conformational footprints

October 18th, 2016 by Buyong Ma

Nature Chemical Biology 12, 890 (2016). doi:10.1038/nchembio.2212

Authors: Buyong Ma & Ruth Nussinov

The mechanisms by which proteins evolve new functions can be slow and mysterious. Comprehensive structural analysis of enzyme variants reveal how gradual enrichments of pre-existing populations with the right productive dynamics for new functions can accomplish this aim.

Insulin signaling: At a snail’s pace

October 18th, 2016 by Stéphane Larochelle

Nature Chemical Biology 12, 889 (2016). doi:10.1038/nchembio.2221

Author: Stéphane Larochelle

Structural basis of nonribosomal peptide macrocyclization in fungi

October 17th, 2016 by Jinru Zhang

Nature Chemical Biology 12, 1001 (2016). doi:10.1038/nchembio.2202

Authors: Jinru Zhang, Nicholas Liu, Ralph A Cacho, Zhou Gong, Zhu Liu, Wenming Qin, Chun Tang, Yi Tang & Jiahai Zhou

Nonribosomal peptide synthetases (NRPSs) in fungi biosynthesize important pharmaceutical compounds, including penicillin, cyclosporine and echinocandin. To understand the fungal strategy of forging the macrocyclic peptide linkage, we determined the crystal structures of the terminal condensation-like (CT) domain and the holo thiolation (T)-CT complex of Penicillium aethiopicum TqaA. The first, to our knowledge, structural depiction of the terminal module in a fungal NRPS provides a molecular blueprint for generating new macrocyclic peptide natural products.

Discovery of MRSA active antibiotics using primary sequence from the human microbiome

October 17th, 2016 by John Chu

Nature Chemical Biology 12, 1004 (2016). doi:10.1038/nchembio.2207

Authors: John Chu, Xavier Vila-Farres, Daigo Inoyama, Melinda Ternei, Louis J Cohen, Emma A Gordon, Boojala Vijay B Reddy, Zachary Charlop-Powers, Henry A Zebroski, Ricardo Gallardo-Macias, Mark Jaskowski, Shruthi Satish, Steven Park, David S Perlin, Joel S Freundlich & Sean F Brady

Here we present a natural product discovery approach, whereby structures are bioinformatically predicted from primary sequence and produced by chemical synthesis (synthetic-bioinformatic natural products, syn-BNPs), circumventing the need for bacterial culture and gene expression. When we applied the approach to nonribosomal peptide synthetase gene clusters from human-associated bacteria, we identified the humimycins. These antibiotics inhibit lipid II flippase and potentiate β-lactam activity against methicillin-resistant Staphylococcus aureus in mice, potentially providing a new treatment regimen.

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Identification and characterization of PPARα ligands in the hippocampus

October 17th, 2016 by Avik Roy

Nature Chemical Biology 12, 1075 (2016). doi:10.1038/nchembio.2204

Authors: Avik Roy, Madhuchhanda Kundu, Malabendu Jana, Rama K Mishra, Yeni Yung, Chi-Hao Luan, Frank J Gonzalez & Kalipada Pahan

  • Posted in Nat Chem Biol, Publications
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